PROJECT ABSTRACT To advance the health and care of children, as in eMERGE II & III, CCHMC will assemble a birth cohort in eMERGE IV, ascertained on pregnant or recently delivered self-identified African-American (AA) women and their babies, along with the willing fathers and siblings. The eMERGE IV collection will be the inaugural effort in a new CCHMC initiative, a birth cohort of mother and baby dyads called My Genome and Me, Cincinnati (MGMC), conceived to develop an understanding of the genomics that informs health and disease risk, beginning at birth and continuing across the lifespan with dyads randomized at enrollment to genotyping with return of results as neonates or later as older children. Our eMERGE IV project will directly grapple with the ethical issues raised by return of results to families with different considerations operating in babies, siblings and parents regarding the particular phenotypes being studied. For eMERGE IV, as site-specific phenotypes, we nominate Asthma, Atopic Dermatitis, Obesity, Hypercholesterolemia, Hypertension, Prematurity, and Breast Cancer. We will exploit the work done that will enable developing polygenic risk scores (PRSs) and genomic risk estimates (GREs) for these conditions in addition to the 15 others chosen by the eMERGE IV Network and anticipate developing consensus across the Network for the PRSs and GREs applied. The care of families will exploit the harmonization of the electronic health records between the adult and pediatric hospitals, which has been achieved with the Maternal and Infant Data Hub (MIDH) using the Observational Medical Outcomes Partnership (OMOP) common data model. For data quality control we will evaluate discrepancies between eMERGE IV genotyping and low read depth coverage (LRDC) genotypes (LRDC sequencing will be at CCHMC expense.) We will collect preferences and attitudes of our local AA community with respect to genomic results and return of results. We will develop health risk-reducing recommendations and return GREs with and without actionable PRSs to assess the influence of PRSs on the adherence to risk-mitigating recommendations. We will use SMART on FHIR (Substitutable Medical Applications, Reusable Technologies and Fast Healthcare Interoperability Resource) through the electronic health record (EHR)-integrated clinical decision support (CDS)-Hooks framework to provide CDS to both the adult and pediatric EHR systems. We will periodically revise PRSs and GREs and return changes when indicated. CCHMC will provide LRDC sequencing from >17,000 DNA AA samples from children in the CCHMC biobank and ?50,000 subjects in total for genotype generation and mitochondrial DNA variant analysis. Federated geocoding will be available to all eMERGE IV sites from CCHMC. To disseminate genomic practice within CCHMC, across the Network, and in general, CCHMC will provide services to advance PRSs and GREs for specific conditions, starting with acute lymphoblastic leukemia, migraine headache, and suicide. In sum, CCHMC presents an aggressive program use genomic medicine to advance toward better health outcomes focused on underserved AA dyads of neonates and mothers with their families.